Basal glucocortcioids increase with age, and have negative feedback impairments. Healthy older human’s basal glucocortcioids levels are not different from college aged males, although they are a little bit higher during the evening. Adults with higher levels of CORT (in their daily fluctuations), have diminished hippocampal-dependent memory consolidation (Lupien et al, 1998). There are other stress related responses that decrease in age as well. In response to infection, the response of immune system to that challenge is blunted in aged organisms as compared to younger, in humans as well as rodents. Repair mechanisms following injuring take longer to have affect in aged versus younger organisms. Following a “temperature challenge”, it takes aged animals longer to return their body temperature to baseline levels. Older rats in an animal field show less locomotion and more stress when exposed to a novel environment in an open field test.
Humans in response to survey type questions indicate a heightened level of stress when faced with novel situations. Following a stressor, physiologically it takes longer for levels of noepinephrine and epinephrine to return to baseline levels, and the responsiveness of the heart and blood vessels are somewhat diminished. If you inject tumor cells into young and old rats, tumor grow faster in old rats. However, if you inject glucocorticoids in rats in response to stressors in young rats, then the tumor rates in both age cohorts are the same. We know that glucocorticoids inhibit the immune system, so differences in glucorcoticoids may be responsible for the tumor growth differences. There is evidence that enlarged adrenal glands, peptic ulcers, and reduced HPC volume, signs of chornic stress, can lead to death at a very young age in vervet monkeys (Uno et al, 1989).
This brings up the glucocorticoid endangerment hypothesis. In the presence of glucocorticoids, neurons are believed to be more vulnerable to some other toxin or extrinsic injury, “metabolic insults”. Glucocorticoids downregulate glucose tranporter gene expression, which inhibits glucose transport, and reduces their metabolic capacity. This might mean that the neuron has a greater probability of necrosis. This action is relatively rapid, as only 24 hour exposure either in vitro or in vivo will compromise cell survival.
Low, basal levels of glucocorticoids play a facilitative role in mitochondrial oxidation. However, very high levels of glucocorticoids lead to a reduced ability for neurons to perform ATP production, which neurons do a huge amount of simply to fuel their ion channels. This is an example of the classic inverted U-shaped dose dependent response curve. The glucocorticoid interacts with an anti-apoptic protein, BCL2, in order to produce this effect, which is a little bit weird, but there is also a U-shaped dose-dependent response curve of % cell death (in vitro, using TUNEL assay) following kainic acid exposure (Du et al, 2009), such that low levels of glucocorticoids may be “neuroprotective.” Many of genes upregulated following glucocorticoid exposure in the aging hippocampus are in the astrocytes, whereas most of the genes being downregulated are in neurons. Astrocytic proliferation may play a role in deleteriously reacting with the neurons following injuries to form glial scars, and perhaps that process can be intervened with genetically.
Lupien et al 1999. S.J. Lupien, C.J. Gillin and R.L. Hauger , Working memory is more sensitive than declarative memory to the acute effects of corticosteroids: A dose-response study in humans. Behav Neurosci 113 (1999), pp. 420–430.
Uno H, Tarara R, Else JG, Suleman MA, Sapolsky RM (1989) Hippocampal damage associated with prolonged and fatal stress in primates. J Neurosci 9:1705–1711.
Du, J. et al. Dynamic regulation of mitochondrial function by glucocorticoids. Proc. Natl Acad. Sci. USA 106, 3543–3548 (2009).
Hormones and Aging, 1995. Google Books.